New Knowledge About CCR5, HIV Infection, and Disease Progression: Is “Old” Still Valuable?

Mehlotra, Rajeev K.

doi:10.1089/aid.2020.0060

Cited by 7 publications

(6 citation statements)

References 29 publications

(51 reference statements)

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“…CCR5 D32 is a common mutation in CCR5 that can lead to a change in protein function and the loss of HIV co-receptor function. Several studies have shown that the CCR5D32 gene locus can effectively control infection (99)(100)(101)(102). In addition, some research results (103) indicate that the expression of CXCR2, CXCR4, and CCR5 are significantly changed in the peripheral blood mDC and pDC of HIV+ progressors.…”

Section: The Relationship Between Soluble Factors Co-receptors and Di...mentioning

confidence: 99%

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

Shi

Chen

et al. 2022

Front. Immunol.

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The natural process of human immunodeficiency virus type 1(HIV-1) infection is characterized by high viral load, immune cell exhaustion, and immunodeficiency, which eventually leads to the stage of acquired immunodeficiency syndrome (AIDS) and opportunistic infections. Rapidly progressing HIV-1 individuals often die of AIDS several years after infection without treatment. The promotion of ART greatly prolongs the survival time of HIV-infected persons. However, some patients have incomplete immune function reconstruction after ART due to latent storage of HIV-infected cells. Therefore, how to achieve a functional cure has always been the focus and hot spot of global AIDS research. Fortunately, the emergence of ECs/LTNPs who can control virus replication naturally has ignited new hope for realizing a functional cure for AIDS. Recently, a special category of infected individuals has attracted attention that can delay the progression of the disease more rigorously than the natural progression of HIV-1 infection described above. These patients are characterized by years of HIV-1 infection, long-term asymptomatic status, and normal CD4+T cell count without ART, classified as HIV-infected long-term nonprogressors (LTNPs) and elite controllers (ECs). Numerous studies have shown that the host and virus jointly determine the progression of HIV-1 infection, in which the level of innate immunity activation plays an important role. As the first line of defense against pathogen invasion, innate immunity is also a bridge to induce adaptive immunity. Compared with natural progressors, innate immunity plays an antiviral role in HIV-1 infection by inducing or activating many innate immune-related factors in the natural ECs. Learning the regulation of ECs immunity, especially the innate immunity in different characteristics, and thus studying the mechanism of the control of disease progression naturally, will contribute to the realization of the functional cure of AIDS. Therefore, this review will explore the relationship between innate immunity and disease progression in ECs of HIV-1 infection from the aspects of innate immune cells, signaling pathways, cytokines, which is helpful to provide new targets and theoretical references for the functional cure, prevention and control of AIDS, and development of a vaccine.

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Section: The Relationship Between Soluble Factors Co-receptors and Di...mentioning

confidence: 99%

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

Shi

Chen

et al. 2022

Front. Immunol.

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“…Our findings also indicated no significant difference in IFN-γ expression level between the two groups of patients. In line with this finding, it has been shown that IFN-γ has no direct antiviral activity against HIV-1 infection in primary cultures, as supported by the in vivo findings of IFN-γ therapy in infected subjects [ 10 , 23 ] . In contrast, certain studies have reported that this cytokine can increase the cytotoxic T lymphocytes and natural killer cell activities against HIV-1-infected cells.…”

Section: Discussionmentioning

confidence: 60%

Immune-Related Gene Profile in HIV-Infected Patients with Discordant Immune Response

Hamidi

Aliasgari

Basimi

et al. 2022

IBJ

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Background:In spite of many reports on persistent low CD4 T cell counts and change in immune-related gene expression level in patients with HIV infection, there is still uncertainty about significant association between gene expression level and HIV infection in patients with and without DIR. The aim of this study was to compare the expression level of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes in HIV-1-positive patients with and without DIR. Methods: In this study, 30 HIV-1-positive patients (15 patients with and 15 patients without DIR [control group]) were included. PBMCs of the patients were collected through density radient centrifugation with Ficoll-Hypaque. RNeasy Plus Mini kit was used to extract RNA. Relative expression levels of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes were evaluated by real-time PCR. The data were analyzed using one-way ANOVA.Results: CD4 T cell counts were significantly lower in DIR patients than the control group (p < 0.01). While there was no significant difference in the relative expression levels of CD4, CCL5, IFN-γ, STAT1, CD45, and ICAM-1 between patients with DIR and control group, APOBEC3G expression level was significantly higher in the patients with DIR as compare to the control group (p < 0.01). Conclusion: Our findings suggest a significantly higher APOBEC3G expression level in patients with DIR, suggesting the potential role of APOBEC3G in patients with immunological discordance besides its suppressing role in HIV-1 infection. Confirmation of this hypothesis requires further research.

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“…The major co-receptor -CCR5-provides natural resistance to HIV infection with 32bp deletion in both alleles (1,2). Recent studies showed gene modification and cell engineering of CCR5 can also induce resistance to HIV infection (10,(13)(14)(15)(16). Finding a suitable donor with HLA-matched by Δ32 target genotype is one of the challenges in allogeneic transplantation (17).…”

Section: Discussionmentioning

confidence: 99%

Distribution of CCR5 Δ32 HIV-1 resistance allele frequency at Zanjan province in Iran

et al. 2021

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Introduction: The CC chemokine receptor 5 (CCR5) is known as the main co-receptor in human immunodeficiency virus (HIV) infection. Accumulating evidence verified 32bp deletion in both alleles of CCR5 provides natural resistance to HIV infection. Accordingly, recent therapeutic approaches are based on gene and cell therapies by inducing this resistance. Allogeneic transplantation of stem cells with CCR5Δ32 homozygous to HIV infected people has been considered as an efficient strategy. Objectives: The aim of this study was to determine CCR5 Δ32 mutation frequency in healthy and HIV-infected individuals in Zanjan province, in Iran and also detecting appropriate candidate for future therapeutic approaches. Patients and Methods: In this study, blood samples were collected from 102 HIV infected patients and 204 healthy controls in ethylene diamine tetra-acetic acid (EDTA) pre-coated tubes. DNA extraction was performed and analyzed for CCR5Δ32 mutation by GAP-PCR in both groups and followed by 2% gel agarose electrophoresis. The Δ32 genotype frequency was statistically determined. Results: Our finding demonstrated that 3 HIV infected patients displayed CCR5 mutation, while 204 healthy controls showed one CCR5 Δ32/Δ32 homozygote mutation. We observed that Δ32 mutation frequency is 0.82% in Zanjan province (χ2 =47.58, P<0.001). Conclusion: Reduction in CCR5 mutation frequency as well as the other polymorphisms related to HIV resistance, can lead to the development of HIV infection epidemiology. Migration, natural selection and genetic admixture can elucidate various distribution of Δ32 allele frequency in different populations, like as north Europeans that reduce gradually to south. The result of this study can facilitate the presentation of suitable Δ32 donors to HIV infected patients in therapeutic approaches.

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New Knowledge About CCR5, HIV Infection, and Disease Progression: Is “Old” Still Valuable?

Cited by 7 publications

References 29 publications

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

Immune-Related Gene Profile in HIV-Infected Patients with Discordant Immune Response

Distribution of CCR5 Δ32 HIV-1 resistance allele frequency at Zanjan province in Iran

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